{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:43:04Z","timestamp":1790678584130,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100004595","name":"Universiti Sains Malaysia","doi-asserted-by":"publisher","award":["1001\/PPSP\/812070"],"award-info":[{"award-number":["1001\/PPSP\/812070"]}],"id":[{"id":"10.13039\/501100004595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients has emerged as a significant clinical problem. The observation that increased epigenetic silencing of potential tumor suppressor genes correlates with disease progression in some CML patients treated with IM suggests a relationship between epigenetic silencing and resistance development. We hypothesize that promoter hypermethylation of<jats:italic>HOXA4<\/jats:italic>could be an epigenetic mechanism mediating IM resistance in CML patients. Thus a study was undertaken to investigate the promoter hypermethylation status of<jats:italic>HOXA4<\/jats:italic>in CML patients on IM treatment and to determine its role in mediating resistance to IM. Genomic DNA was extracted from peripheral blood samples of 95 CML patients (38 good responders and 57 resistant) and 12 normal controls. All samples were bisulfite treated and analysed by methylation-specific high-resolution melt analysis. Compared to the good responders, the<jats:italic>HOXA4<\/jats:italic>hypermethylation level was significantly higher (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.002<\/mml:mn><\/mml:mrow><\/mml:math>) in IM-resistant CML patients. On comparing the risk,<jats:italic>HOXA4<\/jats:italic>hypermethylation was associated with a higher risk for IM resistance (OR 4.658; 95% CI, 1.673\u201312.971;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.003<\/mml:mn><\/mml:mrow><\/mml:math>). Thus, it is reasonable to suggest that promoter hypermethylation of<jats:italic>HOXA4<\/jats:italic>gene could be an epigenetic mechanism mediating IM resistance in CML patients.<\/jats:p>","DOI":"10.1155\/2013\/129715","type":"journal-article","created":{"date-parts":[[2012,12,26]],"date-time":"2012-12-26T16:00:39Z","timestamp":1356537639000},"page":"1-7","source":"Crossref","is-referenced-by-count":25,"title":["<i>HOXA4<\/i>Gene Promoter Hypermethylation as an Epigenetic Mechanism Mediating Resistance to Imatinib Mesylate in Chronic Myeloid Leukemia Patients"],"prefix":"10.1155","volume":"2013","author":[{"given":"Marjanu Hikmah","family":"Elias","sequence":"first","affiliation":[{"name":"Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Health Campus 16150 Kubang Kerian, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Aziz","family":"Baba","sequence":"additional","affiliation":[{"name":"Haemato-Oncology Unit, Department of Internal Medicine, School of Medical Sciences, Universiti Sains Malaysia, Health Campus 16150 Kubang Kerian, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azlan","family":"Husin","sequence":"additional","affiliation":[{"name":"Haemato-Oncology Unit, Department of Internal Medicine, School of Medical Sciences, Universiti Sains Malaysia, Health Campus 16150 Kubang Kerian, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Sulong","sequence":"additional","affiliation":[{"name":"Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Health Campus 16150 Kubang Kerian, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosline","family":"Hassan","sequence":"additional","affiliation":[{"name":"Hematology Department, School of Medical Sciences, Universiti Sains Malaysia, Health Campus 16150 Kubang Kerian, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goh Ai","family":"Sim","sequence":"additional","affiliation":[{"name":"Hospital Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Fadilah","family":"Abdul Wahid","sequence":"additional","affiliation":[{"name":"Medicine Department & Cell Therapy Centre, UKM Medical Centre, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindran","family":"Ankathil","sequence":"additional","affiliation":[{"name":"Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Health Campus 16150 Kubang Kerian, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2006.07.010"},{"issue":"23","key":"2","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1056\/NEJMoa062867","volume":"355","year":"2006","journal-title":"New England Journal of Medicine"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdl273"},{"key":"4","first-page":"219","year":"2006","journal-title":"Hematology"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2010.06.005"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.2174\/156800909789056999"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0919"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022110"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.191"},{"issue":"4","key":"9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.4161\/epi.9020","volume":"4","year":"2009","journal-title":"Epigenetics"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2005.07.003"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-44"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2076"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.4161\/epi.6.3.14038"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2009.01309.x"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404254"},{"issue":"1","key":"17","first-page":"133","volume":"21","year":"2011","journal-title":"Stem Cells and Development"},{"key":"18","volume":"4, article 16","year":"2011","journal-title":"Journal of Ovarian Research"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-08-0466"}],"container-title":["BioMed Research International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2013\/129715.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2013\/129715.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2013\/129715.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T00:51:49Z","timestamp":1498006309000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/bmri\/2013\/129715\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013]]},"references-count":19,"alternative-id":["129715","129715"],"URL":"https:\/\/doi.org\/10.1155\/2013\/129715","relation":{},"ISSN":["2314-6133","2314-6141"],"issn-type":[{"value":"2314-6133","type":"print"},{"value":"2314-6141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013]]}}}